Robert Gross1, Sean Selva1, Alanna Ritchie1, Stefan Sillau1
1University of Colorado
Objective:
To compare changes in plasma concentrations of Neurofilament light (NfL) and Glial Fibrillary Acidic Protein (GFAP) in individuals with relapsing multiple sclerosis (RMS) vs progressive multiple sclerosis (PMS), beginning treatment with anti-CD20 immunotherapy (rituximab or ocrelizumab)
Background:
NfL and GFAP have emerged as promising MS biomarkers easily measured in blood by single molecule array (SIMOA). In MS, high NfL levels correlate with recent disease activity and PMS phenotype, predict future brain atrophy and clinical disability, and are reduced by disease-modifying therapies. Combining NfL and GFAP may have greater prognostic ability than NfL alone.
Design/Methods:
Subjects were selected by MS diagnosis, anti-CD20 treatment for at least 6 months, and presence of multiple blood samples in our Biorepository. Demographic/clinical information was extracted by chart review. SIMOA plasma assays of NfL and GFAP were conducted at baseline and follow-up (between 3 and 12 months) on Quanterix SR-X. Biomarker concentrations were log transformed. Summary statistics and longitudinal regression analyses were generated.
Results:
50 patients (RMS=29, PMS=21) and 94 samples were analyzed. 68% were female, mean age was 45.8(13.5) years, and mean follow-up time was 6.4(0.8) months. n=13(44.8%) RMS and n=1(4.8%) PMS patients had disease activity in the prior 6 months(p=0.0018). Mean(95%CI) NfL concentrations for RMS and PMS fell from 4.7 (3.5-6.3) to 3.4 (2.6-4.3) and from 7.3 (4.6-11.6) to 6.2 (4.3-8.9), respectively. GFAP levels remained stable for RMS and PMS. Differences in follow-up levels between RMS and PMS were statistically significant.
Conclusions:
6 months after initiating anti-CD20 therapy, plasma NfL levels decreased in a cohort of MS patients by an average of 22.2%, with greater reduction in PMS (28.1%) than in RMS (15.8%). Plasma GFAP levels remained stable on average in both RMS and PMS. Results suggest that GFAP, an astrocytic marker, may be a more stable marker of disease progression than NfL in treated MS patients.